MEMORANDUM

To: Margaret Sheppard, U.S. EPA

CC: Bella Maranion and Melissa Fiffer, U.S. EPA

From: Jenny Tanphanich, Kara Altshuler, Reva Rubenstein, and Mark Wagner, ICF 

International 

Date: February 4, 2013

Re: Review and Recommendation for Response to Adverse Comment on C7 Fluoroketone 

as a Halon 1211 Alternative (EPA Contract Number EP-W-10-031 Task Order 105, 

Task 01 and Task Order 205, Task 01)

This document does not contain Clean Air Act (CAA) Confidential Business Information (CBI) 

and, therefore, may be disclosed to the public.

ICF has reviewed comments specific to the proposed use of C7 FK as a streaming agent 

in EPA's Proposed Rule: Protection of Stratospheric Ozone: Listing of Substitutes for 

Ozone-Depleting Substances – Fire Suppression and Explosion Protection (September 

2012). This memorandum summarizes ICF's responses to these comments and 

suggestions for future actions by the SNAP office.

The remainder of this memorandum is organized into the following sections: 

 Section 1: Introduction; 

 Section 2: Chemistry of C7 FK;

 Section 3: Toxicity of C7 FK;

 Section 4: Suggestions for Further Action; and

 Section 5: References.

Please contact Kara Altshuler at 508-540-1774 or Mark Wagner at 202-862-1155 with 

any questions or comments.
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1. Introduction

In July of 2012, ICF submitted risk screens on the acceptability of use of C7 FK,

submitted to the SNAP office by 3M, as a substitute for Halon 1211 in fire protection 

streaming applications. The final risk screen discussed the atmospheric effects of the 

compound, including its global warming potential (GWP), ozone depletion potential

(ODP), and atmospheric lifetime (ALT), and compared those parameters with Halon 

1211 and two currently acceptable substitutes (i.e., HCFC-123 and HFC-236fa). In 

addition, a discussion of the potential health effects of C7 FK was presented, which 

included exposure assessments for varying end users, such as occupational workers. 

Health effects were evaluated via a review of available toxicity studies using animal 

models, and an acceptable exposure limit (AEL) for occupational workers was developed 

based on that review and using accepted risk assessment methodologies developed by 

EPA. The decision by EPA that C7 FK was acceptable for use as a streaming agent was 

based in part on this risk screen.

EPA's Proposed Rule: Protection of Stratospheric Ozone: Listing of Substitutes for 

Ozone-Depleting Substances – Fire Suppression and Explosion Protection (September 

2012) included C7 FK for use as a streaming agent. A public comment posted in 

response to this proposed rule was made which questioned the potential toxicity of C7 FK

based on the ability of some fluorinated ketones to react in the aqueous layer of human or 

animal tissues and exert toxicity. The remainder of this memorandum addresses the 

supporting scientific literature and relevant background documents germane to assessing 

the raised concern of potential toxicity.

2. Chemistry of C7 FK

C7 FK is a mixture of isomers with the following chemical formula, C7F14O:3-pentanone, 

1,1,1,2,4,5,5,5-octafluoro-2,4-bis(trifluoromethyl) and 3-pentanone, 1, 1, 1, 2, 4, 4, 5, 5, 

6, 6, 6-undecafluoro-2,4-bis(trifluoromethyl), with the octofluoro isomer representing 

60% of the total mixture by weight (ICF 2012). 

Ketones, starting with the simplest one (acetone), are susceptible to hydrolysis. In the 

case of acetone, substitution of fluorines for hydrogens, giving hexafluoroacetone (HFA), 

makes the compound more electrophilic, shifting the equilibrium dramatically to one that 

favors formation of a gem-diol hydrate (equilibrium constant of 106vs. 10-3 with 

acetone). This is because fluorine is highly electronegative, thereby making C-O bonds 

more susceptible to nucleophilic attack. This characteristic for reactivity in halogenated 

ketones is cited by J.L. Adcock in a public comment in response to the proposed rule 

(Adcock 2012). Adcock comments on the reactivity of C7 FK, and stresses the expected 
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ability of its two main components (listed above) to react "...with water...to form a 

perfluorinated 'gem-diol'1of low volatility, moderate acidity, and significant surface 

active behavior...."

Adcock provides two references to support this expectation of reactivity. One of the 

references is Chapter VI of the textbook Aliphatic Fluorine Compounds (Lovelace et al. 

1958) titled, Ketones, Aldehydes, and Acetals. This chapter, however, focuses 

specifically on ways of creating fluorine-containing organic compounds, including 

ketones, and only says such fluorine-containing ketones have a "high percentage of enol 

content and they easily form stable hydrates." Nothing more specific to the compound in 

question, such as stability or reactivity, is contained within. 

The second reference, Gambaryan et al. (1966) also begins by discussing the vigorous 

reactivity of HFA with water or alcohols, resulting in a hydrate. The article, however, is 

focused on the various fluoro-organic compounds that can be synthesized from 

perfluorinated compounds and discusses these methodologies in greater detail. As these 

reactions often require harsh methods and solvents (e.g., heat, acids and bases, and 

organometallics), they are not relevant to the conditions in which C7 FK is proposed as a 

substitute for Halon 1211 in streaming applications. The article provides no specific 

information regarding the reactivity or stability of C7 FK. In summary, ICF found that 

both references documented the extreme reactivity of HFA in water, a fact that is 

supported by other sources of chemical information. Adcock suggests that C7 FK is 

expected to react vigorously in water because HFA does so, but the recommended 

references provide no information to support that claim.

In the SNAP materials submitted for C7 FK in the streaming end-use (3M 2010a and 

2010b) and more recent comments (Schultz 2012), 3M provided information that C7 FK

has a very low solubility in water (estimates are on the order of <0.2 mg/mL) and a high 

Henry's Law Constant of 85,100 atm-m

3

/mole. These physical-chemical characteristics 

indicate that the compound, upon release to the environment, will be driven into the 

vapor phase, staying in the atmosphere and not partitioning or dissolving into surface 

water. 

Very little information is available regarding the potential for hydrolysis of highly 

fluorinated compounds. According to 3M, alpha-branched2fluoroketones cannot easily

form hydrate intermediates (e.g., gem-diols) as do smaller perfluorinated ketones, due to 

their structure and low water solubility (Schultz 2012). This argument is supported by 

comparisons of carbon-hydrogen and carbon-fluorine bond lengths. For example, the C-

 

1

Short hand for geminal diol, an organic compound with two hydroxyl functional groups on the 

same carbon atom.

2 Alpha branching indicates that branching of the carbon backbone initiates from the carbon just 

adjacent to the functional carbon (in this case, the ketone carbon).
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H bond length is 106-109 pm, while that of C-F is 133-142 pm. According to 

Lewandowski et al. (2006), fluorine atoms "tightly screen a carbon chain" and make 

perfluorinated compounds highly resistant to hydrolysis, photolysis, microbial 

degradation, and metabolism by vertebrates. In the case of C7 FK, the ketone group is 

shielded by the two -CF3 groups on either side of the oxygen atom, which indicates that 

this alpha-branched perfluoroketone will be similarly resistant to solubility in water (see 

Figure 2).

 

Figure 1. Steric effects of —CH2— and —CF2— bonds (Taken from Lewandowski et al. 2006)

Figure 2. 2D Image of the octofluoro isomer of C7 FK (Taken from ChemSpider 2012)

Additional support for the hydrophobicity of C7 FK is provided by knowledge of the 

solvent dipolarity and polarizability of a compound, which measures the ability of a 

solvent to stabilize a charge or a dipole by virtue of its dielectric effect. As evaluated by 

Kamlet et al. (1983), perfluoro-n-hexane has a dipolarity/polarizability value of -0.4, 

acetone has a value of 0.4, and water has a value of 1.09. Although an imperfect 

surrogate for C7 FK, perfluoro-n-hexane is highly hydrophobic. C7 FK is likely to be 

highly hydrophobic as well, despite the presence of an internal ketone bond (as discussed 

earlier, the presence of so many fluorine atoms in C7 FK should shield the ketone bond 

from attack). The lack of water solubility for C7 FK indicates that it will not form gemdiol hydrates and will thus not have appreciable effects in any organisms that might be 

exposed to it.
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3. Toxicity of C7 FK

In the comment to the Proposed Rule, Adcock indicates that the reactivity of 

perfluorinated ketones in water, particularly in tissues in which there is a lung:blood air 

interface (e.g., nose, sinus, trachea along an inhalation portal of entry) may pose 

significant risks to individuals breathing the compound due to interference with proper 

oxygenation of the blood and/or lung edema. Such an effect would be evident in an 

animal toxicity test if it occurred. Two inhalation studies were performed for C7 FK: a 5-

day repeat toxicity study in which study animals were exposed to high concentrations of 

the compound, and a 28-day repeat dose study in which male and female rats were 

exposed to concentrations ≤10,000 ppm for 6 hours per day. The reported LC50 for the 

study was >10,000 ppm, the highest concentration used. More importantly, no inhalation 

portal-of-entry effects were noted in either study.

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 No other observations were reported 

that might indicate any other adverse effects on blood oxygenation or similar 

impairments. The recommended AEL for C7 FK is 225 ppm (ICF 2011), well below the 

10,000 ppm high exposure concentration used in both studies. The animal toxicity data 

do not support the comment by J.L. Adcock that C7 FK is expected to react with water 

to form a stable gem-diol that will exhibit surface active behavior and thus may cause 

significant risk to individuals breathing the compound.

4. Suggestions for Further Action on C7 FK

ICF believes that C7 FK is acceptable for use as a streaming agent. ICF does not believe 

that the AEL or risk screen documents need to be revised to respond to the comments to 

the proposed rule. However, this response document can be used by EPA to further 

support its decision on this proposed end use for C7 FK.

5. References

3M. 2010a. SNAP Submission to EPA for C7 Fluoroketone. February 22, 2010.

3M. 2010b. P-10-135 – C7 Fluoroketone Teleconference EPA/3M Summary. November 22, 

2010.

Adcock JL. 2012. Comment in response to the Proposed Rule: Protection of Stratospheric 

Ozone: Listing of Substitutes for Ozone-Depleting Substances – Fire Suppression and 

Explosion Protection. Document ID: EPA-HQ-OAR-2011-0111-0026. October 22, 2012.

ChemSpider. 2012. Chemical information for 1,1,1,2,4,5,5,5-octafluoro-2,4-

bis(trifluoromethyl)penan-3-one. (Available at http://www.chemspider.com/ChemicalStructure.63134.html)

 

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Portal of entry effects are specifically investigated in acute and short-term inhalation exposure 

studies as the relevant tissues will receive the greatest exposure to the study compound.
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Gambaryan NP, Rokhlin EM, Zeifman YV et al. 1966. Reactions of the carbonyl group in 

fluorinated ketones. Angew Chem Internat Edit 5(11):947-956.

ICF. 2011. Determination of an Acceptable Exposure Limit for C7 Fluoroketone. May 2011. 

Kamlet MJ, Abbout J-L.M., Abraham MH et al. 1983. Linear solvation energy relationships. 23. 

A comprehensive collection of the solvatochromic parameters, π*, α, and ß, and some 

methods for simplifying the generalized solvatochromic equation. J Org Chem 48:2877-

2887.

Lewandowski G, Meissner E. et al. 2006. Special applications of fluorinated organic compounds. 

J Hazard Mater 136(3): 385-391.

Lovelace AM, Rausch DA, and Postelnek W. 1958. Chapter VI. Ketones, Aldehydes and Acetals. 

Aliphatic Fluorine Compounds. New York: Reinhold Publishing Corporation. pp. 180-187.

Schulz JF. 2012. Comments in response to comment submitted by JL Adcock, in response to the 

Proposed Rule: Protection of Stratospheric Ozone: Listing of Substitutes for Ozone-Depleting 

Substances – Fire Suppression and Explosion Protection. November 30, 2012.